NM_001009931.3:c.5244G>C

Variant names:

• chr1-152216385-C-G
• rs201735593
• NM_001009931.3:c.5244G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001009931.3(HRNR):​c.5244G>C​(p.Ser1748Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 55)
  • Exomes 𝑓: 0.0000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.07
• Publications: 0 publications found

Genes affected

HRNR (HGNC:20846): (hornerin) Predicted to enable calcium ion binding activity and transition metal ion binding activity. Involved in cell envelope organization and establishment of skin barrier. Located in cornified envelope; keratohyalin granule; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDST (HGNC:55988): (cervical cancer associated DHX9 suppressive transcript)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-152216385-C-G is Benign according to our data. Variant chr1-152216385-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3770956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.07 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009931.3. 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
	HRNR	NM_001009931.3	MANE Select	c.5244G>C	p.Ser1748Ser	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
	CCDST	NR_186761.1		n.353+26730C>G		intron	N/A
	CCDST	NR_186762.1		n.179+26904C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRNR	ENST00000368801.4	TSL:1 MANE Select	c.5244G>C	p.Ser1748Ser	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
	CCDST	ENST00000420707.5	TSL:5	n.158+26877C>G		intron	N/A
	CCDST	ENST00000593011.5	TSL:4	n.296+47965C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000694 AC: 1 AN: 144186 Hom.: 0 Cov.: 55

Gnomad AFR AF: 0.0000260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 60516 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000413 AC: 6 AN: 1453104 Hom.: 0 Cov.: 112 AF XY: 0.00000415 AC XY: 3 AN XY: 723136

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33120

American (AMR) AF: 0.00 AC: 0 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 85688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5474

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1105544

Other (OTH) AF: 0.00 AC: 0 AN: 59978

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000694 AC: 1 AN: 144186 Hom.: 0 Cov.: 55 AF XY: 0.0000143 AC XY: 1 AN XY: 70018

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000260 AC: 1 AN: 38492

American (AMR) AF: 0.00 AC: 0 AN: 13746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3310

East Asian (EAS) AF: 0.00 AC: 0 AN: 4230

South Asian (SAS) AF: 0.00 AC: 0 AN: 4250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66764

Other (OTH) AF: 0.00 AC: 0 AN: 1956

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		-3.1
Mutation Taster		=100/0	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: rs201735593; hg19: chr1-152188861;