19-11374916-C-T

Variant names:

• chr19-11374916-C-T
• rs755373334
• NM_175871.4:c.236C>T

Variant summary

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

The NM_175871.4(SWSAP1):​c.236C>T​(p.Pro79Leu) 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 1,461,406 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: 0.0000014 (0 hom.)
• Consequence: SWSAP1 NM_175871.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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.236C>T	p.Pro79Leu	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.236C>T	p.Pro79Leu	missense_variant	Exon 1 of 2		NM_175871.4	ENSP00000501355.1
SWSAP1	ENST00000312423.4	c.173C>T	p.Pro58Leu	missense_variant	Exon 1 of 2	1		ENSP00000310008.1
ENSG00000267277	ENST00000590399.2	n.20G>A		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248588 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134970

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: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461406 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727044

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: 0.00000180

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	0.29
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.34
Sift	Benign	0.16	T
Sift4G	Uncertain	0.051	T
Polyphen		0.92	P
Vest4		0.63
MutPred		0.28		Loss of loop (P = 9e-04);
MVP		0.53
MPC		0.79
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.078
gMVP		0.46

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: rs755373334; hg19: chr19-11485592;