chr3-112168889-T-A

Variant names:

• chr3-112168889-T-A
• rs762257130
• NM_183061.3:c.3225A>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_183061.3(SLC9C1):​c.3225A>T​(p.Ile1075Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,439,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SLC9C1 NM_183061.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.885 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9C1	NM_183061.3	c.3225A>T	p.Ile1075Ile	synonymous_variant	Exon 25 of 29	ENST00000305815.10	NP_898884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9C1	ENST00000305815.10	c.3225A>T	p.Ile1075Ile	synonymous_variant	Exon 25 of 29	2	NM_183061.3	ENSP00000306627.5
SLC9C1	ENST00000487372.5	c.3081A>T	p.Ile1027Ile	synonymous_variant	Exon 24 of 28	1		ENSP00000420688.1
SLC9C1	ENST00000471295.1	n.*1554A>T		non_coding_transcript_exon_variant	Exon 18 of 22	5		ENSP00000418371.1
SLC9C1	ENST00000471295.1	n.*1554A>T		3_prime_UTR_variant	Exon 18 of 22	5		ENSP00000418371.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1439320 Hom.: 0 Cov.: 30 AF XY: 0.00000420 AC XY: 3 AN XY: 714970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000362

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.4
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs762257130; hg19: chr3-111887736;