Genetic Variant FAM110D:p.Ala233Val (chr1-26161989-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024869.3(FAM110D):c.698C>T(p.Ala233Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000404 in 1,237,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

FAM110D
NM_024869.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00200

Publications

0 publications found

Variant links:

Genes affected

FAM110D (HGNC:25860): (family with sequence similarity 110 member D)

FAM110D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044730604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024869.3. 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
	FAM110D	NM_024869.3	MANE Select	c.698C>T	p.Ala233Val	missense	Exon 2 of 2	NP_079145.2	Q8TAY7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM110D	ENST00000374268.5	TSL:1 MANE Select	c.698C>T	p.Ala233Val	missense	Exon 2 of 2	ENSP00000363386.3	Q8TAY7
FAM110D	ENST00000880266.1		c.698C>T	p.Ala233Val	missense	Exon 3 of 3	ENSP00000550325.1
FAM110D	ENST00000880267.1		c.698C>T	p.Ala233Val	missense	Exon 3 of 3	ENSP00000550326.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151280

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:

0.000386

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

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1086002

Hom.:

Cov.:

AF XY:

0.00000194

AC XY:

AN XY:

516036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22504

American (AMR)

AF:

0.00

AC:

AN:

8046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13878

East Asian (EAS)

AF:

0.000117

AC:

AN:

25748

South Asian (SAS)

AF:

0.00

AC:

AN:

20808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3116

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

926942

Other (OTH)

AF:

0.00

AC:

AN:

43456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

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:

0.0000132

AC:

AN:

151280

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41288

American (AMR)

AF:

0.00

AC:

AN:

15174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67778

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.26

PhyloP100

0.0020

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.23

REVEL

Benign

0.066

Sift

Benign

0.32

Sift4G

Benign

0.27

Polyphen

0.0080

Vest4

0.048

MutPred

0.067

Loss of helix (P = 0.028)

MVP

0.043

MPC

1.0

ClinPred

0.13

GERP RS

1.1

Varity_R

0.033

gMVP

0.21

Mutation Taster

=93/7

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

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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