rs1875693651

Variant names:

• chr13-69707771-T-A
• rs1875693651
• NM_020866.3:c.2041A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-69707771-T-A
• chr13-69707771-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020866.3(KLHL1):​c.2041A>T​(p.Thr681Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T681A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHL1 NM_020866.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82
• Publications: 0 publications found

Genes affected

KLHL1 (HGNC:6352): (kelch like family member 1) The KLHL1 protein belongs to a family of actin-organizing proteins related to Drosophila Kelch (Nemes et al., 2000 [PubMed 10888605]).[supplied by OMIM, Feb 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL1	NM_020866.3	c.2041A>T	p.Thr681Ser	missense_variant	Exon 10 of 11	ENST00000377844.9	NP_065917.1
KLHL1	NM_001286725.2	c.1858A>T	p.Thr620Ser	missense_variant	Exon 9 of 10		NP_001273654.1
KLHL1	XM_017020678.3	c.1522A>T	p.Thr508Ser	missense_variant	Exon 10 of 11		XP_016876167.1
KLHL1	XM_017020679.2	c.1372A>T	p.Thr458Ser	missense_variant	Exon 10 of 11		XP_016876168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL1	ENST00000377844.9	c.2041A>T	p.Thr681Ser	missense_variant	Exon 10 of 11	1	NM_020866.3	ENSP00000367075.4
KLHL1	ENST00000545028.2	c.1858A>T	p.Thr620Ser	missense_variant	Exon 9 of 10	2		ENSP00000439602.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.35	T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	-0.015	N;.
PhyloP100		7.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.3	N;.
REVEL	Uncertain	0.40
Sift	Benign	0.68	T;.
Sift4G	Benign	0.44	T;T
Polyphen		0.20	B;.
Vest4		0.72
MutPred		0.51		Gain of catalytic residue at A684 (P = 0.0332);.;
MVP		0.77
MPC		0.14
ClinPred		0.82	D
GERP RS		5.4
Varity_R		0.093
gMVP		0.21
Mutation Taster		=65/35	polymorphism

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: rs1875693651; hg19: chr13-70281903;