NM_001890.2:c.259A>T

Variant names:

• chr4-69939191-A-T
• rs200177207
• NM_001890.2:c.259A>T

Variant summary

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

The NM_001890.2(CSN1S1):​c.259A>T​(p.Ile87Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,448,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. I87V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CSN1S1 NM_001890.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 4 publications found

Genes affected

CSN1S1 (HGNC:2445): (casein alpha s1) Predicted to be involved in response to dehydroepiandrosterone; response to estradiol; and response to steroid hormone. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10872069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSN1S1	NM_001890.2	c.259A>T	p.Ile87Phe	missense_variant	Exon 10 of 16	ENST00000246891.9	NP_001881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSN1S1	ENST00000246891.9	c.259A>T	p.Ile87Phe	missense_variant	Exon 10 of 16	1	NM_001890.2	ENSP00000246891.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 244886 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1448416 Hom.: 0 Cov.: 26 AF XY: 0.00000139 AC XY: 1 AN XY: 720762

African (AFR) AF: 0.00 AC: 0 AN: 33042

American (AMR) AF: 0.00 AC: 0 AN: 43942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25826

East Asian (EAS) AF: 0.00 AC: 0 AN: 39432

South Asian (SAS) AF: 0.00 AC: 0 AN: 84692

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102646

Other (OTH) AF: 0.0000167 AC: 1 AN: 59834

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.18
DEOGEN2	Benign	0.070	T;.;.;T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.45	T;T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.67	N;.;.;.;.;.
PhyloP100		3.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N;N;N;N;.;N
REVEL	Benign	0.13
Sift	Uncertain	0.027	D;T;T;T;.;T
Sift4G	Benign	0.12	T;T;T;T;T;D
Polyphen		0.91	P;.;P;.;.;.
Vest4		0.20
MutPred		0.15		Loss of glycosylation at S86 (P = 0.1758);.;Loss of glycosylation at S86 (P = 0.1758);.;.;.;
MVP		0.55
MPC		0.045
ClinPred		0.22	T
GERP RS		5.1
PromoterAI		-0.0046	Neutral
Varity_R		0.092
gMVP		0.016

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: rs200177207; hg19: chr4-70804909;