3-58643714-C-G

Variant names:

• chr3-58643714-C-G
• NM_138805.3:c.270G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138805.3(FAM3D):​c.270G>C​(p.Met90Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM3D NM_138805.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.88
• 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]

FAM3D-AS1 (HGNC:41276): (FAM3D antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.270G>C	p.Met90Ile	missense	Exon 6 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.270G>C	p.Met90Ile	missense	Exon 6 of 10	ENSP00000351632.2	Q96BQ1
	FAM3D	ENST00000876442.1		c.273G>C	p.Met91Ile	missense	Exon 6 of 11	ENSP00000546501.1
	FAM3D	ENST00000876443.1		c.288G>C	p.Met96Ile	missense	Exon 6 of 10	ENSP00000546502.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.56		Gain of catalytic residue at P92 (P = 0.0262)
MVP		0.35
MPC		0.52
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.50
gMVP		0.64
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

hg19: chr3-58629441;