rs660594

chr6-31869473-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A4	NM_025257.3	c.1130+72C>T		intron_variant		ENST00000229729.11
SLC44A4	NM_001178044.2	c.1004+72C>T		intron_variant
SLC44A4	NM_001178045.2	c.902+72C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A4	ENST00000229729.11	c.1130+72C>T		intron_variant		1	NM_025257.3	P1

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

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.810

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.590

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

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.666

Alfa AF: 0.598 Hom.: 31160

Bravo AF: 0.621

Asia WGS AF: 0.626 AC: 2182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.59
Dann	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs660594; hg19: chr6-31837250;