dbSNP rs531865043: FAM3D:p.Arg38Leu (chr3-58653682-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138805.3(FAM3D):c.113G>T(p.Arg38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

FAM3D
NM_138805.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

FAM3D (HGNC:18665): (FAM3 metabolism regulating signaling molecule D) Involved in negative regulation of insulin secretion. Predicted to be located in extracellular region. Predicted to be integral component of membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

FAM3D links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21394676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3D	NM_138805.3 link	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 10	ENST00000358781.7	NP_620160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3D	ENST00000358781.7 link	c.113G>T	p.Arg38Leu	missense_variant	Exon 3 of 10	1	NM_138805.3	ENSP00000351632.2		Q96BQ1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152266

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251092

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152384

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;T;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

2.0

M;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.58

T;.;.

Polyphen

0.89

P;.;.

Vest4

0.51

MutPred

0.46

Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);

MVP

0.57

MPC

0.34

ClinPred

0.91

GERP RS

4.2

Varity_R

0.17

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over