3-197776957-T-G

Variant names:

• chr3-197776957-T-G
• rs139214163
• NM_032288.7:c.687T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032288.7(FYTTD1):​c.687T>G​(p.Ile229Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000898 in 1,612,374 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00095 (1 hom.)
• Consequence: FYTTD1 NM_032288.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• Publications: 5 publications found

Genes affected

FYTTD1 (HGNC:25407): (forty-two-three domain containing 1) Enables mRNA binding activity. Involved in mRNA export from nucleus. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14402127).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032288.7. 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
	FYTTD1	NM_032288.7	MANE Select	c.687T>G	p.Ile229Met	missense	Exon 7 of 9	NP_115664.2
	FYTTD1	NM_001011537.3		c.609T>G	p.Ile203Met	missense	Exon 8 of 10	NP_001011537.2	Q96QD9-2
	FYTTD1	NR_027840.2		n.1160T>G		non_coding_transcript_exon	Exon 7 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYTTD1	ENST00000241502.9	TSL:1 MANE Select	c.687T>G	p.Ile229Met	missense	Exon 7 of 9	ENSP00000241502.3	Q96QD9-1
	FYTTD1	ENST00000966386.1		c.783T>G	p.Ile261Met	missense	Exon 8 of 10	ENSP00000636445.1
	FYTTD1	ENST00000966385.1		c.681T>G	p.Ile227Met	missense	Exon 7 of 9	ENSP00000636444.1

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000463 AC: 116 AN: 250692 AF XY: 0.000413

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000378

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000802

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.000947 AC: 1383 AN: 1460058 Hom.: 1 Cov.: 28 AF XY: 0.000929 AC XY: 675 AN XY: 726362

African (AFR) AF: 0.0000598 AC: 2 AN: 33434

American (AMR) AF: 0.000471 AC: 21 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000291 AC: 25 AN: 85916

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00116 AC: 1289 AN: 1110820

Other (OTH) AF: 0.000696 AC: 42 AN: 60334

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152316 Hom.: 0 Cov.: 31 AF XY: 0.000403 AC XY: 30 AN XY: 74484

African (AFR) AF: 0.0000962 AC: 4 AN: 41568

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000667 Hom.: 1

Bravo AF: 0.000484

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000371 AC: 45

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000983

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.87
MVP		0.18
MPC		0.74
ClinPred		0.15	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.56
Mutation Taster		=80/20	polymorphism

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: rs139214163; hg19: chr3-197503828; COSMIC: COSV106090882; COSMIC: COSV106090882;