19-11374834-G-C

Variant names:

• chr19-11374834-G-C
• rs1968256959
• NM_175871.4:c.154G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_175871.4(SWSAP1):​c.154G>C​(p.Gly52Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SWSAP1 NM_175871.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

Genes affected

SWSAP1 (HGNC:26638): (SWIM-type zinc finger 7 associated protein 1) Enables single-stranded DNA binding activity. Involved in double-strand break repair via homologous recombination and protein stabilization. Part of Shu complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267277 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SWSAP1	NM_175871.4	c.154G>C	p.Gly52Arg	missense_variant	Exon 1 of 2	ENST00000674460.1	NP_787067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SWSAP1	ENST00000674460.1	c.154G>C	p.Gly52Arg	missense_variant	Exon 1 of 2		NM_175871.4	ENSP00000501355.1
SWSAP1	ENST00000312423.4	c.91G>C	p.Gly31Arg	missense_variant	Exon 1 of 2	1		ENSP00000310008.1
ENSG00000267277	ENST00000590399.2	n.102C>G		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461580 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727088

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91G>C (p.G31R) alteration is located in exon 1 (coding exon 1) of the SWSAP1 gene. This alteration results from a G to C substitution at nucleotide position 91, causing the glycine (G) at amino acid position 31 to be replaced by an arginine (R). 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	0.30
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.34
Sift	Benign	0.54	T
Sift4G	Benign	0.81	T
Polyphen		0.44	B
Vest4		0.63
MutPred		0.21		Gain of helix (P = 0.0164);
MVP		0.66
MPC		1.1
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.17
gMVP		0.61

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: rs1968256959; hg19: chr19-11485510; COSMIC: COSV99710346; COSMIC: COSV99710346;