6-31864579-C-CA

Position:

• chr6-31864579-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_025257.3(SLC44A4):​c.2011+72_2011+73insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,216,504 control chromosomes in the GnomAD database, including 1,319 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1273 hom., cov: 28)
  • Exomes 𝑓: 0.12 (46 hom.)
• Consequence: SLC44A4 NM_025257.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.323

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 -10 ACMG points.

• BP6: Variant 6-31864579-C-CA is Benign according to our data. Variant chr6-31864579-C-CA is described in ClinVar as [Benign]. Clinvar id is 1269949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A4	NM_025257.3	c.2011+72_2011+73insT		intron_variant		ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2	c.1885+72_1885+73insT		intron_variant			NP_001171515.1
SLC44A4	NM_001178045.2	c.1783+72_1783+73insT		intron_variant			NP_001171516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11	c.2011+72_2011+73insT		intron_variant		1	NM_025257.3	ENSP00000229729	P1
SLC44A4	ENST00000375562.8	c.1885+72_1885+73insT		intron_variant		2		ENSP00000364712
SLC44A4	ENST00000544672.5	c.1783+72_1783+73insT		intron_variant		2		ENSP00000444109
SLC44A4	ENST00000487680.1	n.101_102insT		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 14386 AN: 129370 Hom.: 1271 Cov.: 28

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.00565

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.0508

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0449

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.123 AC: 134022 AN: 1087096 Hom.: 46 Cov.: 0 AF XY: 0.124 AC XY: 68072 AN XY: 550588

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.0856

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.0984

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.0760

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.111 AC: 14397 AN: 129408 Hom.: 1273 Cov.: 28 AF XY: 0.111 AC XY: 6933 AN XY: 62252

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.0901

Gnomad4 ASJ AF: 0.0508

Gnomad4 EAS AF: 0.0721

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.121

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 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs5875335; hg19: chr6-31832356;