10-15214195-G-A

Variant names:

• chr10-15214195-G-A
• rs3814165
• NM_001010924.2:c.1393C>T

Variant summary

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

The NM_001010924.2(FAM171A1):​c.1393C>T​(p.Pro465Ser) variant causes a missense change. The variant allele was found at a frequency of 0.162 in 1,613,990 control chromosomes in the GnomAD database, including 22,353 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 0.13 (1619 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20734 hom.)
• Consequence: FAM171A1 NM_001010924.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18
• Publications: 27 publications found

Genes affected

FAM171A1 (HGNC:23522): (family with sequence similarity 171 member A1) Involved in regulation of cell shape and stress fiber assembly. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000232739 (HGNC:58382):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017546415).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010924.2. 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
	FAM171A1	NM_001010924.2	MANE Select	c.1393C>T	p.Pro465Ser	missense	Exon 8 of 8	NP_001010924.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM171A1	ENST00000378116.9	TSL:1 MANE Select	c.1393C>T	p.Pro465Ser	missense	Exon 8 of 8	ENSP00000367356.4
	FAM171A1	ENST00000477161.1	TSL:3	n.593C>T		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000232739	ENST00000802946.1		n.138+5524G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19627 AN: 152020 Hom.: 1620 Cov.: 32

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.151 AC: 37885 AN: 251392 AF XY: 0.157

Gnomad AFR exome AF: 0.0337

Gnomad AMR exome AF: 0.0862

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.165 AC: 241731 AN: 1461852 Hom.: 20734 Cov.: 33 AF XY: 0.166 AC XY: 121012 AN XY: 727228

African (AFR) AF: 0.0275 AC: 920 AN: 33478

American (AMR) AF: 0.0922 AC: 4125 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5932 AN: 26136

East Asian (EAS) AF: 0.138 AC: 5478 AN: 39700

South Asian (SAS) AF: 0.169 AC: 14620 AN: 86256

European-Finnish (FIN) AF: 0.151 AC: 8055 AN: 53406

Middle Eastern (MID) AF: 0.208 AC: 1199 AN: 5768

European-Non Finnish (NFE) AF: 0.172 AC: 191126 AN: 1111996

Other (OTH) AF: 0.170 AC: 10276 AN: 60390

GnomAD4 genome AF: 0.129 AC: 19627 AN: 152138 Hom.: 1619 Cov.: 32 AF XY: 0.130 AC XY: 9669 AN XY: 74374

African (AFR) AF: 0.0349 AC: 1451 AN: 41534

American (AMR) AF: 0.133 AC: 2026 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 779 AN: 3464

East Asian (EAS) AF: 0.155 AC: 800 AN: 5166

South Asian (SAS) AF: 0.169 AC: 812 AN: 4806

European-Finnish (FIN) AF: 0.147 AC: 1560 AN: 10588

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11623 AN: 67988

Other (OTH) AF: 0.168 AC: 354 AN: 2112

Alfa AF: 0.164 Hom.: 7401

Bravo AF: 0.124

TwinsUK AF: 0.173 AC: 643

ALSPAC AF: 0.168 AC: 648

ESP6500AA AF: 0.0422 AC: 186

ESP6500EA AF: 0.175 AC: 1504

ExAC AF: 0.150 AC: 18171

Asia WGS AF: 0.159 AC: 551 AN: 3478

EpiCase AF: 0.182

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.080
Sift	Benign	0.22	T
Sift4G	Benign	0.53	T
Polyphen		0.89	P
Vest4		0.14
MPC		0.70
ClinPred		0.030	T
GERP RS		4.3
Varity_R		0.083
gMVP		0.28
Mutation Taster		=95/5	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: rs3814165; hg19: chr10-15256194; COSMIC: COSV65316008;