15-39617851-C-G

Variant names:

• chr15-39617851-C-G
• rs16969386
• NM_152597.5:c.1583G>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.1583G>C​(p.Gly528Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,864 control chromosomes in the GnomAD database, including 16,654 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1368 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15286 hom.)
• Consequence: FSIP1 NM_152597.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 24 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=0.0049873292).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP1	NM_152597.5	MANE Select	c.1583G>C	p.Gly528Ala	missense	Exon 11 of 12	NP_689810.3
	FSIP1	NM_001324338.2		c.1583G>C	p.Gly528Ala	missense	Exon 11 of 12	NP_001311267.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP1	ENST00000350221.4	TSL:1 MANE Select	c.1583G>C	p.Gly528Ala	missense	Exon 11 of 12	ENSP00000280236.3
	FSIP1	ENST00000642527.1		n.392G>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000496642.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18223 AN: 152010 Hom.: 1372 Cov.: 32

Gnomad AFR AF: 0.0532

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.134

GnomAD2 exomes AF: 0.144 AC: 36313 AN: 251310 AF XY: 0.150

Gnomad AFR exome AF: 0.0498

Gnomad AMR exome AF: 0.0920

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.320

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.135 AC: 197911 AN: 1461734 Hom.: 15286 Cov.: 33 AF XY: 0.138 AC XY: 100032 AN XY: 727182

African (AFR) AF: 0.0542 AC: 1815 AN: 33476

American (AMR) AF: 0.0952 AC: 4258 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3565 AN: 26128

East Asian (EAS) AF: 0.343 AC: 13615 AN: 39682

South Asian (SAS) AF: 0.198 AC: 17055 AN: 86254

European-Finnish (FIN) AF: 0.192 AC: 10270 AN: 53414

Middle Eastern (MID) AF: 0.202 AC: 1168 AN: 5768

European-Non Finnish (NFE) AF: 0.123 AC: 137220 AN: 1111904

Other (OTH) AF: 0.148 AC: 8945 AN: 60388

GnomAD4 genome AF: 0.120 AC: 18212 AN: 152130 Hom.: 1368 Cov.: 32 AF XY: 0.126 AC XY: 9364 AN XY: 74366

African (AFR) AF: 0.0531 AC: 2206 AN: 41524

American (AMR) AF: 0.133 AC: 2040 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 470 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1647 AN: 5168

South Asian (SAS) AF: 0.205 AC: 986 AN: 4816

European-Finnish (FIN) AF: 0.199 AC: 2102 AN: 10558

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8276 AN: 68002

Other (OTH) AF: 0.132 AC: 278 AN: 2106

Alfa AF: 0.130 Hom.: 1108

Bravo AF: 0.113

TwinsUK AF: 0.131 AC: 487

ALSPAC AF: 0.124 AC: 479

ESP6500AA AF: 0.0530 AC: 233

ESP6500EA AF: 0.131 AC: 1124

ExAC AF: 0.141 AC: 17185

Asia WGS AF: 0.246 AC: 859 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.064
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.22
MPC		0.25
ClinPred		0.015	T
GERP RS		4.8
Varity_R		0.23
gMVP		0.044
Mutation Taster		=98/2	polymorphism (auto)

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: rs16969386; hg19: chr15-39910052; COSMIC: COSV63223715;