21-30396513-G-T

Position:

• chr21-30396513-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_181599.3(KRTAP13-1):​c.427G>T​(p.Gly143Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRTAP13-1 NM_181599.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

Genes affected

KRTAP13-1 (HGNC:18924): (keratin associated protein 13-1) Hair keratins and hair keratin-associated proteins (KAPs), such as KRTAP13-1, are the main structural proteins of hair fibers (Rogers et al., 2002 [PubMed 12359730]).[supplied by OMIM, Mar 2008]

LOC105372772 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP13-1	NM_181599.3	c.427G>T	p.Gly143Cys	missense_variant	1/1	ENST00000355459.4	NP_853630.2
LOC105372772	XR_937653.3	n.196-3153C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP13-1	ENST00000355459.4	c.427G>T	p.Gly143Cys	missense_variant	1/1	6	NM_181599.3	ENSP00000347635.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.427G>T (p.G143C) alteration is located in exon 1 (coding exon 1) of the KRTAP13-1 gene. This alteration results from a G to T substitution at nucleotide position 427, causing the glycine (G) at amino acid position 143 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.097
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.038	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.74		Loss of disorder (P = 0.1906);
MVP		0.57
MPC		0.82
ClinPred		0.86	D
GERP RS		3.7
Varity_R		0.38
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-31768831;