Genetic Variant FAM72D:p.Asn113Ser (chr1-145103114-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_207418.3(FAM72D):c.338A>G(p.Asn113Ser) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 17)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM72D
NM_207418.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

Publications

0 publications found

Variant links:

Genes affected

FAM72D (HGNC:33593): (family with sequence similarity 72 member D) Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

FAM72D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.21592197).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207418.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FAM72D	NM_207418.3	MANE Select	c.338A>G	p.Asn113Ser	missense	Exon 3 of 4	NP_997301.2
FAM72D	NM_001345942.2		c.338A>G	p.Asn113Ser	missense	Exon 3 of 4	NP_001332871.1
FAM72D	NR_144320.2		n.512A>G		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM72D	ENST00000400889.3	TSL:1 MANE Select	c.338A>G	p.Asn113Ser	missense	Exon 3 of 4	ENSP00000383682.1	Q6L9T8
	FAM72D	ENST00000936347.1		c.218A>G	p.Asn73Ser	missense	Exon 3 of 4	ENSP00000606406.1

Frequencies

GnomAD3 genomes

AF:

0.00000739

AC:

AN:

135288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

7.21e-7

AC:

AN:

1387202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31912

American (AMR)

AF:

0.00

AC:

AN:

42244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25404

East Asian (EAS)

AF:

0.00

AC:

AN:

38996

South Asian (SAS)

AF:

0.00

AC:

AN:

82942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3940

European-Non Finnish (NFE)

AF:

9.51e-7

AC:

AN:

1051038

Other (OTH)

AF:

0.00

AC:

AN:

57674

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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000739

AC:

AN:

135332

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

65084

show subpopulations

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

African (AFR)

AF:

0.0000272

AC:

AN:

36732

American (AMR)

AF:

0.00

AC:

AN:

13048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3234

East Asian (EAS)

AF:

0.00

AC:

AN:

4442

South Asian (SAS)

AF:

0.00

AC:

AN:

3994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62722

Other (OTH)

AF:

0.00

AC:

AN:

1786

⚠️ 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.075

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DEOGEN2

Benign

0.022

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.22

PhyloP100

5.6

PROVEAN

Benign

-0.87

Sift

Benign

0.23

Sift4G

Benign

0.16

Vest4

0.27

gMVP

0.24

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over