rs780937243

Variant names:

• chr12-52691403-G-A
• rs780937243
• NM_175078.3:c.1499C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-52691403-G-A
• chr12-52691403-G-C
• chr12-52691403-G-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.1499C>T​(p.Ala500Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KRT77 NM_175078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.278
• 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=0.08062342).

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.1499C>T	p.Ala500Val	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.1499C>T	p.Ala500Val	missense	Exon 9 of 9	ENSP00000342710.3	Q7Z794
	KRT77	ENST00000553168.1	TSL:1	n.*837C>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000448207.1	F8VS61
	KRT77	ENST00000553168.1	TSL:1	n.*837C>T		3_prime_UTR	Exon 10 of 10	ENSP00000448207.1	F8VS61

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000439 AC: 1 AN: 227540 AF XY: 0.00000798

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000973

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1446752 Hom.: 0 Cov.: 43 AF XY: 0.00000139 AC XY: 1 AN XY: 719402

African (AFR) AF: 0.00 AC: 0 AN: 33268

American (AMR) AF: 0.00 AC: 0 AN: 44136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25668

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 85256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5408

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108540

Other (OTH) AF: 0.00 AC: 0 AN: 59908

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000835 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	8.0
DANN	Benign	0.96
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.28
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.28
Sift	Benign	0.41	T
Sift4G	Benign	0.49	T
Polyphen		0.60	P
Vest4		0.14
MutPred		0.28		Gain of sheet (P = 0.0477)
MVP		0.46
MPC		0.19
ClinPred		0.096	T
GERP RS		-1.1
Varity_R		0.026
gMVP		0.50
Mutation Taster		=99/1	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: rs780937243; hg19: chr12-53085187;