3-112169290-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_183061.3(SLC9C1):c.2958T>A(p.Phe986Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00759 in 1,613,200 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (11 hom., cov: 33)
  • Exomes 𝑓: 0.0077 (59 hom.)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.95

Genes affected

SLC9C1 (HGNC:31401): (solute carrier family 9 member C1) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to act upstream of or within flagellated sperm motility. Predicted to be located in motile cilium. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015887707).
• BP6: Variant 3-112169290-A-T is Benign according to our data. Variant chr3-112169290-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 774845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9C1	NM_183061.3	c.2958T>A	p.Phe986Leu	missense_variant	24/29	ENST00000305815.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9C1	ENST00000305815.10	c.2958T>A	p.Phe986Leu	missense_variant	24/29	2	NM_183061.3	P1
SLC9C1	ENST00000487372.5	c.2814T>A	p.Phe938Leu	missense_variant	23/28	1
SLC9C1	ENST00000471295.1	c.*1287T>A		3_prime_UTR_variant, NMD_transcript_variant	17/22	5

Frequencies

GnomAD3 genomes AF: 0.00615 AC: 936 AN: 152254 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00985

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00641 AC: 1605 AN: 250254 Hom.: 14 AF XY: 0.00631 AC XY: 854 AN XY: 135246

Gnomad AFR exome AF: 0.000801

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00464

Gnomad FIN exome AF: 0.00732

Gnomad NFE exome AF: 0.00991

Gnomad OTH exome AF: 0.00606

GnomAD4 exome AF: 0.00774 AC: 11309 AN: 1460828 Hom.: 59 Cov.: 31 AF XY: 0.00777 AC XY: 5643 AN XY: 726700

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00345

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00477

Gnomad4 FIN exome AF: 0.00758

Gnomad4 NFE exome AF: 0.00893

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.00615 AC: 937 AN: 152372 Hom.: 11 Cov.: 33 AF XY: 0.00632 AC XY: 471 AN XY: 74514

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00719

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00668

Gnomad4 NFE AF: 0.00985

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00832 Hom.: 3

Bravo AF: 0.00528

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00804 AC: 31

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00686 AC: 59

ExAC AF: 0.00641 AC: 778

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 30, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	SLC9C1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.13
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.73	D
MetaRNN	Benign	0.016	T;T
MetaSVM	Uncertain	-0.029	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.011	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;P
Vest4		0.69
MutPred		0.68		Gain of helix (P = 0.0854);.;
MVP		0.59
MPC		0.39
ClinPred		0.054	T
GERP RS		3.4
Varity_R		0.38
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144423530; hg19: chr3-111888137; COSMIC: COSV59892886;