9-133357017-C-T

Variant names:

• chr9-133357017-C-T
• rs1263346594
• NM_017503.5:c.182C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017503.5(SURF2):​c.182C>T​(p.Ala61Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,421,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A61D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SURF2 NM_017503.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21520215).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017503.5. 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
	SURF2	NM_017503.5	MANE Select	c.182C>T	p.Ala61Val	missense	Exon 2 of 6	NP_059973.4
	SURF2	NM_001278928.2		c.182C>T	p.Ala61Val	missense	Exon 2 of 6	NP_001265857.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SURF2	ENST00000371964.5	TSL:1 MANE Select	c.182C>T	p.Ala61Val	missense	Exon 2 of 6	ENSP00000361032.4	Q15527
	SURF2	ENST00000934438.1		c.182C>T	p.Ala61Val	missense	Exon 2 of 7	ENSP00000604497.1
	SURF2	ENST00000875735.1		c.182C>T	p.Ala61Val	missense	Exon 2 of 6	ENSP00000545794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000555 AC: 1 AN: 180020 AF XY: 0.0000103

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: 0.0000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1421018 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 703208

African (AFR) AF: 0.00 AC: 0 AN: 32766

American (AMR) AF: 0.00 AC: 0 AN: 37858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 37724

South Asian (SAS) AF: 0.00 AC: 0 AN: 81022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092766

Other (OTH) AF: 0.00 AC: 0 AN: 58942

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Uncertain	1.0
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.17	N
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.53
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.025
Sift	Benign	0.28	T
Sift4G	Benign	0.27	T
Vest4		0.070
MutPred		0.29		Loss of helix (P = 0.1299)
MVP		0.35
MPC		0.19
ClinPred		0.27	T
GERP RS		2.9
PromoterAI		-0.053	Neutral
gMVP		0.17
Mutation Taster		=95/5	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: rs1263346594; hg19: chr9-136223893;