rs886039242

Variant names:

• chr13-113491225-G-A
• rs886039242
• NM_017905.6:c.-129G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017905.6(SLC9D1):​c.-129G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC9D1 NM_017905.6 5_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.360
• Publications: 1 publications found

Genes affected

SLC9D1 (HGNC:20329): (transmembrane and coiled-coil domains 3) This gene encodes a member of the monovalent cation:proton antiporter 2 (CPA2) family of transporter proteins. Members of this family typically couple the export of monovalent cations, such as potassium or sodium, to the import of protons across cellular membranes. Mutations in this gene have been identified in patients with a rare inherited vision defect, cornea guttata with anterior polar cataract. [provided by RefSeq, Mar 2017]

DCUN1D2 (HGNC:20328): (defective in cullin neddylation 1 domain containing 2) Enables cullin family protein binding activity. Involved in positive regulation of protein neddylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017905.6. 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
	SLC9D1	NM_017905.6	MANE Select	c.-129G>A		5_prime_UTR	Exon 1 of 13	NP_060375.4
	SLC9D1	NM_001349744.2		c.-129G>A		5_prime_UTR	Exon 1 of 12	NP_001336673.1
	SLC9D1	NM_001349742.2		c.-129G>A		5_prime_UTR	Exon 1 of 12	NP_001336671.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCO3	ENST00000434316.7	TSL:1 MANE Select	c.-129G>A		5_prime_UTR	Exon 1 of 13	ENSP00000389399.2	Q6UWJ1-1
	TMCO3	ENST00000375391.5	TSL:1	c.-129G>A		5_prime_UTR	Exon 1 of 8	ENSP00000364540.1	Q6UWJ1-3
	TMCO3	ENST00000955127.1		c.-129G>A		5_prime_UTR	Exon 1 of 14	ENSP00000625186.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		-0.36
PromoterAI		-0.022	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs886039242;

hg19: chr13-114145540;