rs28602591

Variant names:

• chr9-133379795-C-T
• rs28602591
• NM_153710.5:c.174+673C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153710.5(STKLD1):​c.174+673C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0816 in 152,236 control chromosomes in the GnomAD database, including 629 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 0.082 (629 hom., cov: 32)
• Consequence: STKLD1 NM_153710.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 9 publications found

Genes affected

STKLD1 (HGNC:28669): (serine/threonine kinase like domain containing 1) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

STKLD1 Gene-Disease associations (from GenCC):

• polydactyly

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STKLD1	NM_153710.5	c.174+673C>T		intron_variant	Intron 2 of 17	ENST00000371957.4	NP_714921.4
STKLD1	NR_103997.2	n.282+673C>T		intron_variant	Intron 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STKLD1	ENST00000371957.4	c.174+673C>T		intron_variant	Intron 2 of 17	1	NM_153710.5	ENSP00000361025.3
STKLD1	ENST00000468046.1	n.85+673C>T		intron_variant	Intron 1 of 1	3
STKLD1	ENST00000475232.1	n.66+673C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12437 AN: 152118 Hom.: 628 Cov.: 32

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0816 AC: 12429 AN: 152236 Hom.: 629 Cov.: 32 AF XY: 0.0807 AC XY: 6007 AN XY: 74446

African (AFR) AF: 0.0393 AC: 1632 AN: 41552

American (AMR) AF: 0.0795 AC: 1216 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3470

East Asian (EAS) AF: 0.0210 AC: 109 AN: 5180

South Asian (SAS) AF: 0.0989 AC: 477 AN: 4824

European-Finnish (FIN) AF: 0.108 AC: 1143 AN: 10606

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6886 AN: 67986

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.0956 Hom.: 202

Bravo AF: 0.0773

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28602591; hg19: chr9-136246666;