rs247938

Variant names:

• chr5-100563147-T-C
• rs247938
• NM_198507.3:c.569+959T>C

Variant summary

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

The NM_198507.3(FAM174A):​c.569+959T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,762 control chromosomes in the GnomAD database, including 3,644 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 0.21 (3644 hom., cov: 32)
• Consequence: FAM174A NM_198507.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 4 publications found

Genes affected

FAM174A (HGNC:24943): (family with sequence similarity 174 member A) Predicted to be integral component of membrane. [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 (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198507.3. 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
	FAM174A	NM_198507.3	MANE Select	c.569+959T>C		intron	N/A	NP_940909.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM174A	ENST00000312637.5	TSL:1 MANE Select	c.569+959T>C		intron	N/A	ENSP00000307954.2
	FAM174A	ENST00000715272.1		c.569+959T>C		intron	N/A	ENSP00000520441.1
	FAM174A	ENST00000505792.1	TSL:3	n.137+959T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32081 AN: 151644 Hom.: 3644 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0868

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.211 AC: 32092 AN: 151762 Hom.: 3644 Cov.: 32 AF XY: 0.211 AC XY: 15635 AN XY: 74148

African (AFR) AF: 0.262 AC: 10864 AN: 41440

American (AMR) AF: 0.142 AC: 2156 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3462

East Asian (EAS) AF: 0.0870 AC: 449 AN: 5162

South Asian (SAS) AF: 0.155 AC: 748 AN: 4824

European-Finnish (FIN) AF: 0.232 AC: 2445 AN: 10554

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14409 AN: 67808

Other (OTH) AF: 0.186 AC: 389 AN: 2092

Alfa AF: 0.207 Hom.: 1784

Bravo AF: 0.205

Asia WGS AF: 0.115 AC: 400 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.90
PhyloP100		1.5
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: rs247938; hg19: chr5-99898851; COSMIC: COSV57062267;