NM_001009931.3:c.6552C>T

Variant names:

• chr1-152215077-G-A
• rs765143413
• NM_001009931.3:c.6552C>T

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.6552C>T​(p.Ser2184Ser) 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 0.00021 (0 hom., cov: 35)
  • Exomes 𝑓: 0.00017 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: HRNR NM_001009931.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.734
• 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=-0.87).
• BP6: Variant 1-152215077-G-A is Benign according to our data. Variant chr1-152215077-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2639200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.734 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.6552C>T	p.Ser2184Ser	synonymous	Exon 3 of 3	NP_001009931.1	Q86YZ3
	CCDST	NR_186761.1		n.353+25422G>A		intron	N/A
	CCDST	NR_186762.1		n.179+25596G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRNR	ENST00000368801.4	TSL:1 MANE Select	c.6552C>T	p.Ser2184Ser	synonymous	Exon 3 of 3	ENSP00000357791.3	Q86YZ3
	CCDST	ENST00000420707.5	TSL:5	n.158+25569G>A		intron	N/A
	CCDST	ENST00000593011.5	TSL:4	n.296+46657G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000222 AC: 30 AN: 135192 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00121

Gnomad AMR AF: 0.0000715

Gnomad ASJ AF: 0.000304

Gnomad EAS AF: 0.000225

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000943

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00116 AC: 83 AN: 71470 AF XY: 0.000795

Gnomad AFR exome AF: 0.00597

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.000911

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000650

Gnomad NFE exome AF: 0.000272

Gnomad OTH exome AF: 0.00129

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000174 AC: 253 AN: 1454490 Hom.: 1 Cov.: 126 AF XY: 0.000167 AC XY: 121 AN XY: 723758

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

African (AFR) AF: 0.00763 AC: 238 AN: 31210

American (AMR) AF: 0.0000453 AC: 2 AN: 44198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 85922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109030

Other (OTH) AF: 0.000183 AC: 11 AN: 60022

⚠️ 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: 0.000214 AC: 29 AN: 135266 Hom.: 0 Cov.: 35 AF XY: 0.000242 AC XY: 16 AN XY: 66212

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

African (AFR) AF: 0.000548 AC: 18 AN: 32836

American (AMR) AF: 0.0000715 AC: 1 AN: 13994

Ashkenazi Jewish (ASJ) AF: 0.000304 AC: 1 AN: 3294

East Asian (EAS) AF: 0.000225 AC: 1 AN: 4440

South Asian (SAS) AF: 0.00 AC: 0 AN: 4318

European-Finnish (FIN) AF: 0.000101 AC: 1 AN: 9898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 186

European-Non Finnish (NFE) AF: 0.0000943 AC: 6 AN: 63622

Other (OTH) AF: 0.00 AC: 0 AN: 1852

⚠️ 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: 0.000334 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	-0.87
CADD	Benign	3.6
DANN	Benign	0.85
PhyloP100		-0.73
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: rs765143413; hg19: chr1-152187553;