chr3-112169290-A-T

Variant names:

• chr3-112169290-A-T
• rs144423530
• NM_183061.3:c.2958T>A

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 4.95
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 774845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183061.3. 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
	SLC9C1	NM_183061.3	MANE Select	c.2958T>A	p.Phe986Leu	missense	Exon 24 of 29	NP_898884.1	Q4G0N8-1
	SLC9C1	NM_001320531.2		c.2814T>A	p.Phe938Leu	missense	Exon 23 of 28	NP_001307460.1	Q4G0N8-2
	SLC9C1	NR_135297.2		n.2228T>A		non_coding_transcript_exon	Exon 18 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C1	ENST00000305815.10	TSL:2 MANE Select	c.2958T>A	p.Phe986Leu	missense	Exon 24 of 29	ENSP00000306627.5	Q4G0N8-1
	SLC9C1	ENST00000487372.5	TSL:1	c.2814T>A	p.Phe938Leu	missense	Exon 23 of 28	ENSP00000420688.1	Q4G0N8-2
	SLC9C1	ENST00000471295.1	TSL:5	n.*1287T>A		non_coding_transcript_exon	Exon 17 of 22	ENSP00000418371.1	F8WCJ0

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

GnomAD2 exomes AF: 0.00641 AC: 1605 AN: 250254 AF XY: 0.00631

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 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

African (AFR) AF: 0.000598 AC: 20 AN: 33448

American (AMR) AF: 0.00345 AC: 154 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 42 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00477 AC: 411 AN: 86104

European-Finnish (FIN) AF: 0.00758 AC: 404 AN: 53290

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5758

European-Non Finnish (NFE) AF: 0.00893 AC: 9922 AN: 1111610

Other (OTH) AF: 0.00573 AC: 346 AN: 60340

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

African (AFR) AF: 0.00118 AC: 49 AN: 41602

American (AMR) AF: 0.00719 AC: 110 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4828

European-Finnish (FIN) AF: 0.00668 AC: 71 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00985 AC: 670 AN: 68030

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Uncertain	-0.029	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

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