rs114379210

Variant names:

• chr12-52613732-C-A
• rs114379210
• NM_175068.3:c.940G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-52613732-C-A
• chr12-52613732-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_175068.3(KRT73):​c.940G>T​(p.Ala314Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A314T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT73 NM_175068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03
• Publications: 0 publications found

Genes affected

KRT73 (HGNC:28928): (keratin 73) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT73-AS1 (HGNC:49607): (KRT73 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175068.3. 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
	KRT73	NM_175068.3	MANE Select	c.940G>T	p.Ala314Ser	missense	Exon 5 of 9	NP_778238.1	Q86Y46-1
	KRT73-AS1	NR_126005.1		n.2235C>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT73	ENST00000305748.7	TSL:1 MANE Select	c.940G>T	p.Ala314Ser	missense	Exon 5 of 9	ENSP00000307014.3	Q86Y46-1
	KRT73	ENST00000552855.1	TSL:3	c.175G>T	p.Ala59Ser	missense	Exon 2 of 6	ENSP00000449081.1	H0YIC5
	KRT73	ENST00000546934.1	TSL:2	n.965G>T		non_coding_transcript_exon	Exon 5 of 8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		5.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.016	D
Polyphen		0.66	P
Vest4		0.61
MutPred		0.72		Gain of phosphorylation at A314 (P = 0.0259)
MVP		0.57
MPC		0.40
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.29
gMVP		0.48
Mutation Taster		=59/41	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: rs114379210; hg19: chr12-53007516;