rs200062643

Variant names:

• chr19-19297106-C-A
• rs200062643
• NM_172231.4:c.1126G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-19297106-C-A
• chr19-19297106-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_172231.4(SUGP1):​c.1126G>T​(p.Ala376Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. A376T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SUGP1 NM_172231.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

SUGP1 (HGNC:18643): (SURP and G-patch domain containing 1) SF4 is a member of the SURP family of splicing factors.[supplied by OMIM, Sep 2003]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041614085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUGP1	NM_172231.4	c.1126G>T	p.Ala376Ser	missense_variant	Exon 8 of 14	ENST00000247001.10	NP_757386.2
SUGP1	XM_047439142.1	c.496G>T	p.Ala166Ser	missense_variant	Exon 6 of 12		XP_047295098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUGP1	ENST00000247001.10	c.1126G>T	p.Ala376Ser	missense_variant	Exon 8 of 14	1	NM_172231.4	ENSP00000247001.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250446 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135488

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461590 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727096

Gnomad4 AFR exome AF: 0.0000299

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.0
DANN	Benign	0.37
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.26	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.030
Sift	Benign	0.53	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.13
MPC		0.19
ClinPred		0.027	T
GERP RS		0.89
Varity_R		0.038

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: rs200062643; hg19: chr19-19407915;