3-58653682-C-A

Variant names:

• chr3-58653682-C-A
• rs531865043
• NM_138805.3:c.113G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: FAM3D NM_138805.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21394676).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138805.3. 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
	FAM3D	NM_138805.3	MANE Select	c.113G>T	p.Arg38Leu	missense	Exon 3 of 10	NP_620160.1	A0A0A8K9B4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3D	ENST00000358781.7	TSL:1 MANE Select	c.113G>T	p.Arg38Leu	missense	Exon 3 of 10	ENSP00000351632.2	Q96BQ1
	FAM3D	ENST00000876442.1		c.116G>T	p.Arg39Leu	missense	Exon 3 of 11	ENSP00000546501.1
	FAM3D	ENST00000876443.1		c.131G>T	p.Arg44Leu	missense	Exon 3 of 10	ENSP00000546502.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152266 Hom.: 0 Cov.: 33

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: 0.00000398 AC: 1 AN: 251092 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152384 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74518

African (AFR) AF: 0.00 AC: 0 AN: 41604

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Benign	0.21	T
Sift4G	Benign	0.58	T
Polyphen		0.89	P
Vest4		0.51
MutPred		0.46		Loss of MoRF binding (P = 0.0101)
MVP		0.57
MPC		0.34
ClinPred		0.91	D
GERP RS		4.2
Varity_R		0.17
gMVP		0.71
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs531865043; hg19: chr3-58639409; COSMIC: COSV107442781;