NM_152597.5:c.1204T>C

Variant names:

• chr15-39618230-A-G
• rs10152640
• NM_152597.5:c.1204T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152597.5(FSIP1):​c.1204T>C​(p.Cys402Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,601,432 control chromosomes in the GnomAD database, including 84,230 homozygotes. 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. C402Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.40 (14090 hom., cov: 32)
  • Exomes 𝑓: 0.30 (70140 hom.)
• Consequence: FSIP1 NM_152597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 26 publications found

Genes affected

FSIP1 (HGNC:21674): (fibrous sheath interacting protein 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.7889657E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152597.5. 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
	FSIP1	NM_152597.5	MANE Select	c.1204T>C	p.Cys402Arg	missense	Exon 11 of 12	NP_689810.3
	FSIP1	NM_001324338.2		c.1204T>C	p.Cys402Arg	missense	Exon 11 of 12	NP_001311267.1	Q8NA03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP1	ENST00000350221.4	TSL:1 MANE Select	c.1204T>C	p.Cys402Arg	missense	Exon 11 of 12	ENSP00000280236.3	Q8NA03
	FSIP1	ENST00000884361.1		c.1204T>C	p.Cys402Arg	missense	Exon 11 of 12	ENSP00000554420.1
	FSIP1	ENST00000942556.1		c.1045T>C	p.Cys349Arg	missense	Exon 10 of 11	ENSP00000612615.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60292 AN: 152028 Hom.: 14064 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.304 AC: 75150 AN: 247318 AF XY: 0.302

Gnomad AFR exome AF: 0.675

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.346

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.304 AC: 439938 AN: 1449286 Hom.: 70140 Cov.: 32 AF XY: 0.302 AC XY: 217193 AN XY: 719368

African (AFR) AF: 0.675 AC: 22412 AN: 33190

American (AMR) AF: 0.205 AC: 9104 AN: 44466

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7076 AN: 26016

East Asian (EAS) AF: 0.366 AC: 14443 AN: 39434

South Asian (SAS) AF: 0.278 AC: 23836 AN: 85762

European-Finnish (FIN) AF: 0.310 AC: 16517 AN: 53254

Middle Eastern (MID) AF: 0.330 AC: 1779 AN: 5388

European-Non Finnish (NFE) AF: 0.295 AC: 325443 AN: 1101956

Other (OTH) AF: 0.323 AC: 19328 AN: 59820

GnomAD4 genome AF: 0.397 AC: 60364 AN: 152146 Hom.: 14090 Cov.: 32 AF XY: 0.391 AC XY: 29096 AN XY: 74376

African (AFR) AF: 0.661 AC: 27438 AN: 41494

American (AMR) AF: 0.292 AC: 4462 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 946 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1761 AN: 5188

South Asian (SAS) AF: 0.281 AC: 1356 AN: 4822

European-Finnish (FIN) AF: 0.311 AC: 3286 AN: 10582

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19989 AN: 67988

Other (OTH) AF: 0.370 AC: 782 AN: 2114

Alfa AF: 0.322 Hom.: 40031

Bravo AF: 0.407

TwinsUK AF: 0.308 AC: 1141

ALSPAC AF: 0.302 AC: 1163

ESP6500AA AF: 0.639 AC: 2789

ESP6500EA AF: 0.299 AC: 2544

ExAC AF: 0.311 AC: 37673

Asia WGS AF: 0.329 AC: 1149 AN: 3478

EpiCase AF: 0.301

EpiControl AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.5
DANN	Benign	0.58
DEOGEN2	Benign	0.00081	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.070	T
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.042
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.0080
Sift	Benign	0.38	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.0070
MPC		0.043
ClinPred		0.00058	T
GERP RS		-0.45
Varity_R		0.070
gMVP		0.010
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs10152640; hg19: chr15-39910431; COSMIC: COSV63223450;