NM_003047.5:c.2352C>A

Variant names:

• chr1-27100403-G-T
• rs2124123678
• NM_003047.5:c.2352C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 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. 13/22 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Lichtenstein-Knorr syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1096006).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003047.5. 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
	SLC9A1	NM_003047.5	MANE Select	c.2352C>A	p.Asp784Glu	missense	Exon 12 of 12	NP_003038.2
	SLC9A1	NR_046474.2		n.2682C>A		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A1	ENST00000263980.8	TSL:1 MANE Select	c.2352C>A	p.Asp784Glu	missense	Exon 12 of 12	ENSP00000263980.3	P19634-1
	SLC9A1	ENST00000854572.1		c.2352C>A	p.Asp784Glu	missense	Exon 13 of 13	ENSP00000524631.1
	SLC9A1	ENST00000854573.1		c.2187C>A	p.Asp729Glu	missense	Exon 12 of 12	ENSP00000524632.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.5
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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs2124123678; hg19: chr1-27426894;