NM_001141917.2:c.3596A>C

Variant names:

• chr9-34723644-T-G
• NM_001141917.2:c.3596A>C

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]

PHF24 (HGNC:29180): (PHD finger protein 24) Predicted to enable metal ion binding activity. Predicted to act upstream of or within several processes, including detection of mechanical stimulus involved in sensory perception of pain; gamma-aminobutyric acid signaling pathway; and regulation of GABAergic synaptic transmission. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288583 (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 rank	MANE	Protein	UniProt
SPATA31F1	NM_001141917.2	c.3596A>C	p.His1199Pro	missense_variant	Exon 4 of 4	ENST00000378788.4	NP_001135389.1
PHF24	XM_047423102.1	c.133+20606T>G		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1	c.70+20606T>G		intron_variant	Intron 2 of 9		XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM205A	ENST00000378788.4	c.3596A>C	p.His1199Pro	missense_variant	Exon 4 of 4	2	NM_001141917.2	ENSP00000417711.1
ENSG00000288583	ENST00000664167.1	n.86+20606T>G		intron_variant	Intron 1 of 1

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

Jun 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
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;