12-52691972-C-T

Variant names:

• chr12-52691972-C-T
• rs778191928
• NM_175078.3:c.1428G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_175078.3(KRT77):​c.1428G>A​(p.Arg476Arg) variant causes a splice region, synonymous 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT77 NM_175078.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.8532
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.815
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 12-52691972-C-T is Benign according to our data. Variant chr12-52691972-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3289537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.815 with no splicing effect.

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.1428G>A	p.Arg476Arg	splice_region synonymous	Exon 8 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.1428G>A	p.Arg476Arg	splice_region synonymous	Exon 8 of 9	ENSP00000342710.3	Q7Z794
	KRT77	ENST00000553168.1	TSL:1	n.*766G>A		splice_region non_coding_transcript_exon	Exon 9 of 10	ENSP00000448207.1	F8VS61
	KRT77	ENST00000553168.1	TSL:1	n.*766G>A		3_prime_UTR	Exon 9 of 10	ENSP00000448207.1	F8VS61

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.89
PhyloP100		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.85
dbscSNV1_RF	Benign	0.61
SpliceAI score (max)		0.070		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: rs778191928; hg19: chr12-53085756;