1-27100403-G-T

Position:

• chr1-27100403-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_003047.5(SLC9A1):​c.2352C>A​(p.Asp784Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: SLC9A1 NM_003047.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

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]

SLC9A1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC9A1. . Gene score misZ 3.5504 (greater than the threshold 3.09). Trascript score misZ 4.6807 (greater than threshold 3.09). GenCC has associacion of gene with Lichtenstein-Knorr syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.1096006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A1	NM_003047.5	c.2352C>A	p.Asp784Glu	missense_variant	12/12	ENST00000263980.8	NP_003038.2
SLC9A1	XM_011542021.4	c.2022C>A	p.Asp674Glu	missense_variant	13/13		XP_011540323.1
SLC9A1	XM_047428769.1	c.2022C>A	p.Asp674Glu	missense_variant	16/16		XP_047284725.1
SLC9A1	NR_046474.2	n.2682C>A		non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A1	ENST00000263980.8	c.2352C>A	p.Asp784Glu	missense_variant	12/12	1	NM_003047.5	ENSP00000263980.3
SLC9A1	ENST00000374089.5	n.1577C>A		non_coding_transcript_exon_variant	7/7	2
SLC9A1	ENST00000447808.1	n.829C>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2022

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	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.10
Sift	Benign	0.33	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.17		Gain of glycosylation at P786 (P = 0.072);
MVP		0.26
MPC		0.23
ClinPred		0.41	T
GERP RS		3.1
Varity_R		0.030
gMVP		0.16

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: chr1-27426894;