9-81945194-A-C

Variant names:

• chr9-81945194-A-C
• NM_207416.3:c.255A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_207416.3(SPATA31D3):​c.255A>C​(p.Glu85Asp) variant causes a missense 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 11)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.368

Genes affected

SPATA31D3 (HGNC:38603): (SPATA31 subfamily D member 3) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267559 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15974614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D3	NM_207416.3	c.255A>C	p.Glu85Asp	missense_variant	Exon 3 of 4	ENST00000445385.3	NP_997299.2
LOC105376105	NR_188610.1	n.1039+1196T>G		intron_variant	Intron 4 of 5
LOC105376105	NR_188611.1	n.1228+1007T>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31D3	ENST00000445385.3	c.255A>C	p.Glu85Asp	missense_variant	Exon 3 of 4	1	NM_207416.3	ENSP00000488117.1
ENSG00000267559	ENST00000585776.5	n.1039+1196T>G		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome AF: 0.00000204 AC: 2 AN: 981448 Hom.: 0 Cov.: 18 AF XY: 0.00000205 AC XY: 1 AN XY: 486940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000522

GnomAD4 genome Cov.: 11

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 31, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.255A>C (p.E85D) alteration is located in exon 3 (coding exon 3) of the SPATA31D3 gene. This alteration results from a A to C substitution at nucleotide position 255, causing the glutamic acid (E) at amino acid position 85 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.5
DANN	Benign	0.40
DEOGEN2	Benign	0.036	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.16	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.49	T
Sift4G	Benign	0.24	T
Polyphen		0.80	P
Vest4		0.14
GERP RS		-1.2
Varity_R		0.088
gMVP		0.029

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-84560109;