12-52691280-C-A

Variant names:

• chr12-52691280-C-A
• rs763455099
• NM_175078.3:c.1622G>T

Variant summary

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

The NM_175078.3(KRT77):​c.1622G>T​(p.Gly541Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. G541D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRT77 NM_175078.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 0 publications found

Genes affected

KRT77 (HGNC:20411): (keratin 77) 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 an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

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=0.09292495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175078.3. 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
	KRT77	NM_175078.3	MANE Select	c.1622G>T	p.Gly541Val	missense	Exon 9 of 9	NP_778253.2	Q7Z794

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT77	ENST00000341809.8	TSL:1 MANE Select	c.1622G>T	p.Gly541Val	missense	Exon 9 of 9	ENSP00000342710.3	Q7Z794
	KRT77	ENST00000553168.1	TSL:1	n.*960G>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000448207.1	F8VS61
	KRT77	ENST00000553168.1	TSL:1	n.*960G>T		3_prime_UTR	Exon 10 of 10	ENSP00000448207.1	F8VS61

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448218 Hom.: 0 Cov.: 64 AF XY: 0.00 AC XY: 0 AN XY: 719886

African (AFR) AF: 0.00 AC: 0 AN: 33208

American (AMR) AF: 0.00 AC: 0 AN: 43478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25816

East Asian (EAS) AF: 0.00 AC: 0 AN: 39134

South Asian (SAS) AF: 0.00 AC: 0 AN: 85468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104068

Other (OTH) AF: 0.00 AC: 0 AN: 59662

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	11
DANN	Benign	0.84
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.21	T
Sift4G	Uncertain	0.048	D
Polyphen		0.20	B
Vest4		0.24
MutPred		0.37		Gain of sheet (P = 0.0101)
MVP		0.47
MPC		0.24
ClinPred		0.14	T
GERP RS		0.35
Varity_R		0.079
gMVP		0.57
Mutation Taster		=95/5	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: rs763455099; hg19: chr12-53085064;