rs660594

Variant names:

• chr6-31869473-G-A
• rs660594
• NM_025257.3:c.1130+72C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_025257.3(SLC44A4):​c.1130+72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,314,934 control chromosomes in the GnomAD database, including 217,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (27963 hom., cov: 33)
  • Exomes 𝑓: 0.56 (189738 hom.)
• Consequence: SLC44A4 NM_025257.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.435
• Publications: 39 publications found

Genes affected

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC44A4 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 72

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-31869473-G-A is Benign according to our data. Variant chr6-31869473-G-A is described in ClinVar as Benign. ClinVar VariationId is 1281145.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025257.3. 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
	SLC44A4	NM_025257.3	MANE Select	c.1130+72C>T		intron	N/A	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.1004+72C>T		intron	N/A	NP_001171515.1	Q53GD3-4
	SLC44A4	NM_001178045.2		c.902+72C>T		intron	N/A	NP_001171516.1	A0A1U9X8K7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.1130+72C>T		intron	N/A	ENSP00000229729.6	Q53GD3-1
	SLC44A4	ENST00000414427.1	TSL:5	c.779+72C>T		intron	N/A	ENSP00000398901.1	H0Y5I3
	SLC44A4	ENST00000882851.1		c.1130+72C>T		intron	N/A	ENSP00000552910.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91184 AN: 151954 Hom.: 27936 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.565 AC: 656844 AN: 1162864 Hom.: 189738 Cov.: 16 AF XY: 0.571 AC XY: 333483 AN XY: 584050

African (AFR) AF: 0.677 AC: 18362 AN: 27134

American (AMR) AF: 0.650 AC: 23011 AN: 35422

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 18835 AN: 23258

East Asian (EAS) AF: 0.630 AC: 22063 AN: 35034

South Asian (SAS) AF: 0.664 AC: 49258 AN: 74154

European-Finnish (FIN) AF: 0.431 AC: 20788 AN: 48180

Middle Eastern (MID) AF: 0.793 AC: 3853 AN: 4858

European-Non Finnish (NFE) AF: 0.545 AC: 471108 AN: 864678

Other (OTH) AF: 0.590 AC: 29566 AN: 50146

GnomAD4 genome AF: 0.600 AC: 91270 AN: 152070 Hom.: 27963 Cov.: 33 AF XY: 0.597 AC XY: 44365 AN XY: 74342

African (AFR) AF: 0.672 AC: 27873 AN: 41490

American (AMR) AF: 0.642 AC: 9817 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2815 AN: 3468

East Asian (EAS) AF: 0.599 AC: 3090 AN: 5162

South Asian (SAS) AF: 0.642 AC: 3096 AN: 4824

European-Finnish (FIN) AF: 0.429 AC: 4535 AN: 10570

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37883 AN: 67956

Other (OTH) AF: 0.666 AC: 1403 AN: 2106

Alfa AF: 0.589 Hom.: 51848

Bravo AF: 0.621

Asia WGS AF: 0.626 AC: 2182 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.65
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs660594; hg19: chr6-31837250; COSMIC: COSV107214185; COSMIC: COSV107214185;