Genetic Variant NM_144664.5:c.628A>G (chr11-95779671-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_144664.5(FAM76B):c.628A>G(p.Thr210Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,610,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

FAM76B
NM_144664.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.278

Publications

1 publications found

Variant links:

Genes affected

FAM76B (HGNC:28492): (family with sequence similarity 76 member B) Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

FAM76B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030553877).

BP6

Variant 11-95779671-T-C is Benign according to our data. Variant chr11-95779671-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3092516.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144664.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM76B	NM_144664.5	MANE Select	c.628A>G	p.Thr210Ala	missense	Exon 7 of 10	NP_653265.3
	FAM76B	NM_001330357.2		c.628A>G	p.Thr210Ala	missense	Exon 7 of 10	NP_001317286.1	F5GX09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM76B	ENST00000358780.10	TSL:1 MANE Select	c.628A>G	p.Thr210Ala	missense	Exon 7 of 10	ENSP00000351631.5	Q5HYJ3-1
FAM76B	ENST00000398187.6	TSL:1	n.628A>G		non_coding_transcript_exon	Exon 7 of 11	ENSP00000381248.2	Q5HYJ3-3
FAM76B	ENST00000543641.5	TSL:1	n.628A>G		non_coding_transcript_exon	Exon 7 of 12	ENSP00000444087.1	Q5HYJ3-3

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000243

AC:

AN:

247258

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000280

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000960

AC:

AN:

1458366

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33298

American (AMR)

AF:

0.00

AC:

AN:

44434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25982

East Asian (EAS)

AF:

0.000203

AC:

AN:

39450

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53090

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110238

Other (OTH)

AF:

0.0000166

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151772

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74136

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000192

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67726

Other (OTH)

AF:

0.00

AC:

AN:

2082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.011

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.18

M_CAP

Benign

0.0015

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.28

PrimateAI

Benign

0.47

PROVEAN

Benign

0.29

REVEL

Benign

0.073

Sift

Benign

0.68

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.13

MutPred

0.12

Loss of phosphorylation at T210 (P = 0.0517)

MVP

0.21

MPC

0.26

ClinPred

0.017

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.26

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over