9-133360004-G-T

Variant names:

• chr9-133360004-G-T
• rs149969130
• NM_017503.5:c.392G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017503.5(SURF2):​c.392G>T​(p.Arg131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SURF2 NM_017503.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

Genes affected

SURF2 (HGNC:11475): (surfeit 2) This gene shares a bidirectional promoter with surfeit 1 (SURF1; GeneID: 6834), which is located on the opposite strand. It encodes a conserved protein that is expressed in a variety of tissues. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3513024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SURF2	NM_017503.5	c.392G>T	p.Arg131Leu	missense_variant	Exon 4 of 6	ENST00000371964.5	NP_059973.4
SURF2	NM_001278928.2	c.392G>T	p.Arg131Leu	missense_variant	Exon 4 of 6		NP_001265857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SURF2	ENST00000371964.5	c.392G>T	p.Arg131Leu	missense_variant	Exon 4 of 6	1	NM_017503.5	ENSP00000361032.4
SURF2	ENST00000486887.1	n.294G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
SURF2	ENST00000495524.5	n.573G>T		non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1450494 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 720782

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: 0.00000181

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.88
FATHMM_MKL	Uncertain	0.81	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.097
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Vest4		0.36
MutPred		0.66		Loss of MoRF binding (P = 0.0195);
MVP		0.28
MPC		0.30
ClinPred		0.43	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs149969130; hg19: chr9-136226880;