9-34723296-G-T

Variant names:

• chr9-34723296-G-T
• rs546555671
• NM_001141917.2:c.3944C>A

Variant summary

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

The NM_001141917.2(SPATA31F1):​c.3944C>A​(p.Pro1315His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000047 in 1,551,694 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (1 hom.)
• Consequence: SPATA31F1 NM_001141917.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.506
• Publications: 0 publications found

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]

ENSG00000230074 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0139377415).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141917.2. 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
	SPATA31F1	NM_001141917.2	MANE Select	c.3944C>A	p.Pro1315His	missense	Exon 4 of 4	NP_001135389.1	Q6ZU69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31F1	ENST00000378788.4	TSL:2 MANE Select	c.3944C>A	p.Pro1315His	missense	Exon 4 of 4	ENSP00000417711.1	Q6ZU69
	ENSG00000230074	ENST00000664167.1		n.86+20258G>T		intron	N/A
	ENSG00000230074	ENST00000837930.1		n.174+20258G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152186 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: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000960 AC: 15 AN: 156246 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 68 AN: 1399390 Hom.: 1 Cov.: 65 AF XY: 0.0000695 AC XY: 48 AN XY: 690206

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.000745 AC: 59 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49270

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5698

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078968

Other (OTH) AF: 0.0000517 AC: 3 AN: 58000

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74484

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000477 AC: 12

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.51
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.11		Loss of loop (P = 0.0603)
MVP		0.21
ClinPred		0.66	D
GERP RS		-2.0
Varity_R		0.093
gMVP		0.11
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: rs546555671; hg19: chr9-34723293;