21-30613795-C-A

Variant names:

• chr21-30613795-C-A
• rs145876389
• NM_181602.2:c.110G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181602.2(KRTAP6-1):​c.110G>T​(p.Cys37Phe) 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 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 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. C37Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRTAP6-1 NM_181602.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 0 publications found

Genes affected

KRTAP6-1 (HGNC:18931): (keratin associated protein 6-1) Predicted to be involved in keratinization. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000308278 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084733844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181602.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP6-1	NM_181602.2	MANE Select	c.110G>T	p.Cys37Phe	missense	Exon 1 of 1	NP_853633.1	Q3LI64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP6-1	ENST00000329122.2	TSL:6 MANE Select	c.110G>T	p.Cys37Phe	missense	Exon 1 of 1	ENSP00000332690.2	Q3LI64
	ENSG00000308278	ENST00000832954.1		n.176-6034C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461376 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726980

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111578

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.4
DANN	Benign	0.85
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.75
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.12
Sift4G	Benign	0.68	T
Polyphen		0.020	B
Vest4		0.29
MutPred		0.20		Gain of sheet (P = 0.0344)
MVP		0.18
MPC		0.22
ClinPred		0.12	T
GERP RS		1.2
PromoterAI		-0.0080	Neutral
Varity_R		0.47
gMVP		0.043
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs145876389; hg19: chr21-31986114;