21-41348672-T-C

Position:

• chr21-41348672-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_058186.4(FAM3B):​c.566T>C​(p.Val189Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM3B NM_058186.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

Genes affected

FAM3B (HGNC:1253): (FAM3 metabolism regulating signaling molecule B) Involved in insulin secretion. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33290598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM3B	NM_058186.4	c.566T>C	p.Val189Ala	missense_variant	7/8	ENST00000357985.7
FAM3B	NM_206964.2	c.422T>C	p.Val141Ala	missense_variant	6/7
FAM3B	XM_011529649.3	c.608T>C	p.Val203Ala	missense_variant	7/8
FAM3B	XM_011529648.3	c.566T>C	p.Val189Ala	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM3B	ENST00000357985.7	c.566T>C	p.Val189Ala	missense_variant	7/8	1	NM_058186.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.32	T;.;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L;.;.;.
MutationTaster	Benign	0.79	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.090	T;D;T;T
Sift4G	Benign	0.099	T;T;T;T
Polyphen		0.62	P;.;B;P
Vest4		0.40
MutPred		0.50		.;.;.;Gain of disorder (P = 0.0791);
MVP		0.26
MPC		0.15
ClinPred		0.69	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-42720599;