1-27100354-G-A

Variant names:

• chr1-27100354-G-A
• NM_003047.5:c.2401C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003047.5(SLC9A1):​c.2401C>T​(p.His801Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,405,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC9A1 NM_003047.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

Genes affected

SLC9A1 (HGNC:11071): (solute carrier family 9 member A1) This gene encodes a Na+/H+ antiporter that is a member of the solute carrier family 9. The encoded protein is a plasma membrane transporter that is expressed in the kidney and intestine. This protein plays a central role in regulating pH homeostasis, cell migration and cell volume. This protein may also be involved in tumor growth. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08382812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A1	NM_003047.5	c.2401C>T	p.His801Tyr	missense_variant	Exon 12 of 12	ENST00000263980.8	NP_003038.2
SLC9A1	XM_011542021.4	c.2071C>T	p.His691Tyr	missense_variant	Exon 13 of 13		XP_011540323.1
SLC9A1	XM_047428769.1	c.2071C>T	p.His691Tyr	missense_variant	Exon 16 of 16		XP_047284725.1
SLC9A1	NR_046474.2	n.2731C>T		non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A1	ENST00000263980.8	c.2401C>T	p.His801Tyr	missense_variant	Exon 12 of 12	1	NM_003047.5	ENSP00000263980.3
SLC9A1	ENST00000374089.5	n.1626C>T		non_coding_transcript_exon_variant	Exon 7 of 7	2
SLC9A1	ENST00000447808.1	n.878C>T		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1405606 Hom.: 0 Cov.: 38 AF XY: 0.00000289 AC XY: 2 AN XY: 692744

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: 0.00000277

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 05, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.022
Sift	Benign	0.036	D
Sift4G	Benign	0.066	T
Polyphen		0.061	B
Vest4		0.23
MutPred		0.26		Gain of phosphorylation at H801 (P = 0.0096);
MVP		0.17
MPC		0.28
ClinPred		0.091	T
GERP RS		2.6
Varity_R		0.035
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-27426845;