rs7655841

chr4-128969635-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144643.4(SCLT1):c.777+743A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,010 control chromosomes in the GnomAD database, including 6,836 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6836 hom., cov: 32)
• Consequence: SCLT1 NM_144643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

Genes affected

SCLT1 (HGNC:26406): (sodium channel and clathrin linker 1) This gene encodes an adaptor protein. Studies of a related gene in rat suggest that the encoded protein functions to link clathrin to the sodium channel protein type 10 subunit alpha protein. The encoded protein has also been identified as a component of distal appendages of centrioles that is necessary for ciliogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCLT1	NM_144643.4	c.777+743A>G		intron_variant		ENST00000281142.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCLT1	ENST00000281142.10	c.777+743A>G		intron_variant		2	NM_144643.4	P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40153 AN: 151892 Hom.: 6840 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.271

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.264 AC: 40187 AN: 152010 Hom.: 6836 Cov.: 32 AF XY: 0.260 AC XY: 19324 AN XY: 74334

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.270

Alfa AF: 0.225 Hom.: 802

Bravo AF: 0.288

Asia WGS AF: 0.201 AC: 700 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.6
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs7655841; hg19: chr4-129890790;