NM_005556.4:c.44C>A

Variant names:

• chr12-52233340-C-A
• NM_005556.4:c.44C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005556.4(KRT7):​c.44C>A​(p.Ala15Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT7 NM_005556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

Genes affected

KRT7 (HGNC:6445): (keratin 7) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
KRT7	NM_005556.4	c.44C>A	p.Ala15Asp	missense_variant	Exon 1 of 9	ENST00000331817.6	NP_005547.3
KRT7	XM_011538325.3	c.44C>A	p.Ala15Asp	missense_variant	Exon 1 of 8		XP_011536627.1
KRT7	XM_047428827.1	c.44C>A	p.Ala15Asp	missense_variant	Exon 1 of 7		XP_047284783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT7	ENST00000331817.6	c.44C>A	p.Ala15Asp	missense_variant	Exon 1 of 9	1	NM_005556.4	ENSP00000329243.5
KRT7	ENST00000546666.1	n.192C>A		non_coding_transcript_exon_variant	Exon 2 of 2	4
KRT7	ENST00000552400.1	n.*192C>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44C>A (p.A15D) alteration is located in exon 1 (coding exon 1) of the KRT7 gene. This alteration results from a C to A substitution at nucleotide position 44, causing the alanine (A) at amino acid position 15 to be replaced by an aspartic acid (D). 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	0.22
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.016
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.22	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.018	D
Sift4G	Benign	0.18	T
Polyphen		0.93	P
Vest4		0.48
MutPred		0.22		Loss of MoRF binding (P = 0.0355);
MVP		0.62
MPC		0.55
ClinPred		0.52	D
GERP RS		3.9
Varity_R		0.36
gMVP		0.60

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: chr12-52627124;