9-34723644-T-G

Position:

• chr9-34723644-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001141917.2(SPATA31F1):​c.3596A>C​(p.His1199Pro) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA31F1 NM_001141917.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.180

Genes affected

SPATA31F1 (HGNC:41911): (SPATA31 subfamily F member 1) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10409504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA31F1	NM_001141917.2	c.3596A>C	p.His1199Pro	missense_variant	4/4	ENST00000378788.4	NP_001135389.1
PHF24	XM_047423102.1	c.133+20606T>G		intron_variant			XP_047279058.1
PHF24	XM_047423103.1	c.70+20606T>G		intron_variant			XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA31F1	ENST00000378788.4	c.3596A>C	p.His1199Pro	missense_variant	4/4	2	NM_001141917.2	ENSP00000417711	P1
	ENST00000664167.1	n.86+20606T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2023

The c.3596A>C (p.H1199P) alteration is located in exon 4 (coding exon 4) of the FAM205A gene. This alteration results from a A to C substitution at nucleotide position 3596, causing the histidine (H) at amino acid position 1199 to be replaced by a proline (P). 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	0.074
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.0
DANN	Benign	0.63
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.011
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.030	D
Polyphen		0.011	B
Vest4		0.40
MutPred		0.27		Gain of loop (P = 0.0166);
MVP		0.081
ClinPred		0.12	T
GERP RS		-4.1
Varity_R		0.12
gMVP		0.043

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-34723641;