chr20-45723995-C-T

Variant names:

• chr20-45723995-C-T
• rs200862274
• NM_178455.3:c.231C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_178455.3(SPINT4):​c.231C>T​(p.Asn77Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,458,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SPINT4 NM_178455.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

Genes affected

SPINT4 (HGNC:16130): (serine peptidase inhibitor, Kunitz type 4) Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178455.3. 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
	SPINT4	NM_178455.3	MANE Select	c.231C>T	p.Asn77Asn	synonymous	Exon 2 of 3	NP_848550.1	Q6UDR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINT4	ENST00000279058.4	TSL:1 MANE Select	c.231C>T	p.Asn77Asn	synonymous	Exon 2 of 3	ENSP00000279058.3	Q6UDR6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1458028 Hom.: 0 Cov.: 34 AF XY: 0.00000827 AC XY: 6 AN XY: 725274

African (AFR) AF: 0.0000303 AC: 1 AN: 33002

American (AMR) AF: 0.00 AC: 0 AN: 43850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 85258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1110926

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.9
DANN	Benign	0.61
PhyloP100		1.1

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: rs200862274; hg19: chr20-44352634;