3-184338313-G-C

Variant names:

• chr3-184338313-G-C
• rs1881973
• NM_144635.5:c.89-74G>C

Variant summary

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

The NM_144635.5(FAM131A):​c.89-74G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,382,302 control chromosomes in the GnomAD database, including 102,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13371 hom., cov: 31)
  • Exomes 𝑓: 0.38 (89345 hom.)
• Consequence: FAM131A NM_144635.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• Publications: 10 publications found

Genes affected

FAM131A (HGNC:28308): (family with sequence similarity 131 member A)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144635.5. 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
	FAM131A	NM_144635.5	MANE Select	c.89-74G>C		intron	N/A	NP_653236.3
	FAM131A	NM_001171093.2		c.-25+942G>C		intron	N/A	NP_001164564.1	Q6UXB0-2
	FAM131A	NM_001366134.1		c.-167-74G>C		intron	N/A	NP_001353063.1	Q6UXB0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131A	ENST00000383847.7	TSL:2 MANE Select	c.89-74G>C		intron	N/A	ENSP00000373360.2	Q6UXB0-3
	FAM131A	ENST00000340957.9	TSL:1	c.-25+942G>C		intron	N/A	ENSP00000340974.5	Q6UXB0-2
	FAM131A	ENST00000855138.1		c.89-74G>C		intron	N/A	ENSP00000525197.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62812 AN: 151660 Hom.: 13358 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.379 AC: 466395 AN: 1230524 Hom.: 89345 AF XY: 0.378 AC XY: 224899 AN XY: 595348

African (AFR) AF: 0.446 AC: 11614 AN: 26016

American (AMR) AF: 0.570 AC: 8627 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 8463 AN: 17736

East Asian (EAS) AF: 0.418 AC: 13141 AN: 31440

South Asian (SAS) AF: 0.320 AC: 17884 AN: 55964

European-Finnish (FIN) AF: 0.406 AC: 12204 AN: 30096

Middle Eastern (MID) AF: 0.449 AC: 2268 AN: 5052

European-Non Finnish (NFE) AF: 0.372 AC: 371695 AN: 998260

Other (OTH) AF: 0.403 AC: 20499 AN: 50832

GnomAD4 genome AF: 0.414 AC: 62859 AN: 151778 Hom.: 13371 Cov.: 31 AF XY: 0.414 AC XY: 30727 AN XY: 74140

African (AFR) AF: 0.454 AC: 18785 AN: 41358

American (AMR) AF: 0.524 AC: 7988 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3468

East Asian (EAS) AF: 0.408 AC: 2090 AN: 5120

South Asian (SAS) AF: 0.311 AC: 1495 AN: 4808

European-Finnish (FIN) AF: 0.391 AC: 4116 AN: 10534

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25558 AN: 67926

Other (OTH) AF: 0.430 AC: 905 AN: 2106

Alfa AF: 0.261 Hom.: 594

Bravo AF: 0.430

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		2.2
Mutation Taster		=100/0	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: rs1881973; hg19: chr3-184056101; COSMIC: COSV59993325; COSMIC: COSV59993325;