14-20556460-A-T

Variant names:

• chr14-20556460-A-T
• rs1243647
• NM_001110356.2:c.607T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001110356.2(RNASE9):​c.607T>A​(p.Ser203Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNASE9 NM_001110356.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 0 publications found

Genes affected

RNASE9 (HGNC:20673): (ribonuclease A family member 9 (inactive)) Predicted to enable nucleic acid binding activity. Predicted to act upstream of or within positive regulation of flagellated sperm motility involved in capacitation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0547356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110356.2. 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
	RNASE9	NM_001110356.2	MANE Select	c.607T>A	p.Ser203Thr	missense	Exon 3 of 3	NP_001103826.2	A0AAG2RNW0
	RNASE9	NM_001110358.1		c.625T>A	p.Ser209Thr	missense	Exon 4 of 4	NP_001103828.1	P60153-2
	RNASE9	NM_001110359.1		c.625T>A	p.Ser209Thr	missense	Exon 5 of 5	NP_001103829.1	P60153-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE9	ENST00000554964.6	TSL:1 MANE Select	c.607T>A	p.Ser203Thr	missense	Exon 3 of 3	ENSP00000450599.2	A0AAG2RNW0
	RNASE9	ENST00000404716.7	TSL:1	c.625T>A	p.Ser209Thr	missense	Exon 5 of 5	ENSP00000384683.3	P60153-2
	RNASE9	ENST00000553706.5	TSL:1	c.625T>A	p.Ser209Thr	missense	Exon 5 of 5	ENSP00000450570.1	P60153-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1453828 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723438

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 85854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105250

Other (OTH) AF: 0.00 AC: 0 AN: 60070

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.22
DANN	Benign	0.72
DEOGEN2	Benign	0.00062	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.23
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.015
Sift	Benign	0.20	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.29		Gain of catalytic residue at P205 (P = 0.0028)
MVP		0.12
MPC		0.079
ClinPred		0.087	T
GERP RS		-1.1
Varity_R		0.040
gMVP		0.17
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: rs1243647; hg19: chr14-21024619;