NM_058186.4:c.619A>T

Variant names:

• chr21-41357108-A-T
• rs183635372
• NM_058186.4:c.619A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_058186.4(FAM3B):​c.619A>T​(p.Ile207Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,611,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I207M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: FAM3B NM_058186.4 missense, splice_region
• Scores: Splicing: ADA: 0.0002334
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04486087).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058186.4. 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
	FAM3B	NM_058186.4	MANE Select	c.619A>T	p.Ile207Phe	missense splice_region	Exon 8 of 8	NP_478066.3
	FAM3B	NM_206964.2		c.475A>T	p.Ile159Phe	missense splice_region	Exon 7 of 7	NP_996847.1	P58499-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3B	ENST00000357985.7	TSL:1 MANE Select	c.619A>T	p.Ile207Phe	missense splice_region	Exon 8 of 8	ENSP00000350673.2	P58499-1
	FAM3B	ENST00000398652.7	TSL:1	c.736A>T	p.Ile246Phe	missense splice_region	Exon 9 of 9	ENSP00000381646.3	P58499-2
	FAM3B	ENST00000398647.7	TSL:1	c.475A>T	p.Ile159Phe	missense splice_region	Exon 7 of 7	ENSP00000381642.3	P58499-3

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152226 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: 0.00154

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: 0.000156 AC: 39 AN: 249858 AF XY: 0.000141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00213

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1458746 Hom.: 0 Cov.: 29 AF XY: 0.0000220 AC XY: 16 AN XY: 725814

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.000933 AC: 37 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 85826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110228

Other (OTH) AF: 0.0000166 AC: 1 AN: 60242

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74510

African (AFR) AF: 0.00 AC: 0 AN: 41570

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

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

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000824 AC: 10

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	0.59
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Benign	0.73
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.48
MVP		0.66
MPC		0.58
ClinPred		0.31	T
GERP RS		3.7
Varity_R		0.20
gMVP		0.68
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.010		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: rs183635372; hg19: chr21-42729035;