7-143356630-C-T

Variant names:

• chr7-143356630-C-T
• rs17854363
• NM_001031690.3:c.1003G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031690.3(FAM131B):​c.1003G>A​(p.Ala335Thr) variant causes a missense change. The variant allele was found at a frequency of 0.195 in 1,613,588 control chromosomes in the GnomAD database, including 32,438 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.18 (2868 hom., cov: 31)
  • Exomes 𝑓: 0.20 (29570 hom.)
• Consequence: FAM131B NM_001031690.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 21 publications found

Genes affected

FAM131B (HGNC:22202): (family with sequence similarity 131 member B) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013714731).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031690.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131B	NM_001031690.3	MANE Select	c.1003G>A	p.Ala335Thr	missense	Exon 7 of 7	NP_001026860.2
	FAM131B	NM_001371248.1		c.967G>A	p.Ala323Thr	missense	Exon 6 of 6	NP_001358177.1
	FAM131B	NM_001371250.1		c.919G>A	p.Ala307Thr	missense	Exon 7 of 7	NP_001358179.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131B	ENST00000443739.7	TSL:1 MANE Select	c.1003G>A	p.Ala335Thr	missense	Exon 7 of 7	ENSP00000410603.2
	FAM131B	ENST00000409222.7	TSL:1	c.919G>A	p.Ala307Thr	missense	Exon 7 of 7	ENSP00000387147.3
	FAM131B	ENST00000409408.5	TSL:1	c.919G>A	p.Ala307Thr	missense	Exon 6 of 6	ENSP00000387017.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28061 AN: 151748 Hom.: 2868 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.214 AC: 53932 AN: 251432 AF XY: 0.212

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.196 AC: 285847 AN: 1461720 Hom.: 29570 Cov.: 34 AF XY: 0.195 AC XY: 141748 AN XY: 727176

African (AFR) AF: 0.114 AC: 3822 AN: 33478

American (AMR) AF: 0.258 AC: 11523 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 8672 AN: 26136

East Asian (EAS) AF: 0.353 AC: 14032 AN: 39700

South Asian (SAS) AF: 0.163 AC: 14045 AN: 86256

European-Finnish (FIN) AF: 0.267 AC: 14285 AN: 53410

Middle Eastern (MID) AF: 0.210 AC: 1212 AN: 5768

European-Non Finnish (NFE) AF: 0.185 AC: 206223 AN: 1111858

Other (OTH) AF: 0.199 AC: 12033 AN: 60390

GnomAD4 genome AF: 0.185 AC: 28069 AN: 151868 Hom.: 2868 Cov.: 31 AF XY: 0.189 AC XY: 13997 AN XY: 74214

African (AFR) AF: 0.118 AC: 4907 AN: 41442

American (AMR) AF: 0.205 AC: 3132 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1472 AN: 5142

South Asian (SAS) AF: 0.154 AC: 738 AN: 4794

European-Finnish (FIN) AF: 0.277 AC: 2925 AN: 10544

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13085 AN: 67908

Other (OTH) AF: 0.195 AC: 410 AN: 2102

Alfa AF: 0.198 Hom.: 10585

Bravo AF: 0.181

TwinsUK AF: 0.186 AC: 691

ALSPAC AF: 0.184 AC: 709

ESP6500AA AF: 0.124 AC: 546

ESP6500EA AF: 0.193 AC: 1662

ExAC AF: 0.211 AC: 25567

Asia WGS AF: 0.205 AC: 714 AN: 3478

EpiCase AF: 0.200

EpiControl AF: 0.202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.080
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.070
Sift	Benign	0.35	T
Sift4G	Benign	0.55	T
Polyphen		0.20	B
Vest4		0.10
MPC		0.66
ClinPred		0.0085	T
GERP RS		5.8
Varity_R		0.054
gMVP		0.041
Mutation Taster		=99/1	polymorphism (auto)

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

dbSNP: rs17854363; hg19: chr7-143053723; COSMIC: COSV58368750; COSMIC: COSV58368750;